[Treatment of spontaneous intracranial hypotension by epidural saline infusion]. / Traitement de l'hypotension spontanée du liquide cérébrospinal par perfusion épidurale de sérum salé isotonique.

INTRODUCTION: Spontaneous intracranial hypotension (SIH) is an uncommon cause of secondary headache due to a cerebrospinal fluid (CSF) hypotension. Lumbar epidural blood-patch (LEBP) is the most effective treatment and can be repeated in case of relapse. There is no standard therapeutic strategy for patients free of dural tears who fail to respond to several consecutive blood-patches. We report two cases of SIH successfully treated by an epidural saline infusion after two consecutive LEBP. CASE REPORTS: A 35-year-old woman was admitted to hospital for severe orthostatic headache. The diagnosis of SIH was retained. Two LEBP were performed but with no clinical benefit. Headache disappeared totally after an epidural saline infusion. A second woman, aged 75 years, was admitted for chronic orthostatic headaches. The CSF pressure was low. Search for a dural tear was negative. After two unsuccessful LEBPs, the patient was treated with an epidural saline infusion. Her headache resolved completely and definitely. DISCUSSION: It is common procedure to search for a dural tear when patients fail to respond to several consecutive LEPB. Surgical repair is however exceptional. An epidural saline infusion might be an efficient therapeutic alternative despite the small number of cases reported in the literature.

Recurrence of the T666M calcium channel CACNA1A gene mutation in familial hemiplegic migraine with progressive cerebellar ataxia.

Familial hemiplegic migraine (HM) is an autosomal dominant migraine with aura. In 20% of HM families, HM is associated with a mild permanent cerebellar ataxia (PCA). The CACNA1A gene encoding the alpha1A subunit of P/Q-type voltage-gated calcium channels is involved in 50% of unselected HM families and in all families with HM/PCA. Four CACNA1A missense mutations have been identified in HM: two in pure HM and two in HM/PCA. Different CACNA1A mutations have been identified in other autosomal dominant conditions: mutations leading to a truncated protein in episodic ataxia type 2 (EA2), small expansions of a CAG trinucleotide in spinocerebellar ataxia type 6 and also in three families with EA2 features, and, finally, a missense mutation in a single family suffering from episodic ataxia and severe progressive PCA. We screened 16 families and 3 nonfamilial case patients affected by HM/PCA for specific CACNA1A mutations and found nine families and one nonfamilial case with the same T666M mutation, one new mutation (D715E) in one family, and no CAG repeat expansion. Both T666M and D715E substitutions were absent in 12 probands belonging to pure HM families whose disease appears to be linked to CACNA1A. Finally, haplotyping with neighboring markers suggested that T666M arose through recurrent mutational events. These data could indicate that the PCA observed in 20% of HM families results from specific pathophysiologic mechanisms.

Mapping of a complicated familial spastic paraplegia to locus SPG4 on chromosome 2p.

Autosomal dominant familial spastic paraplegia (AD-FSP) is a degenerative disorder of the central motor system characterised by progressive spasticity of the lower limbs. AD-FSP has been divided into pure and complicated forms. Pure AD-FSP is genetically heterogeneous; three loci have been mapped to chromosomes 14q (SPG3), 2p (SPG4), and 15q (SPG6), whereas no loci responsible for complicated forms have been identified to date. Here we report linkage to the SPG4 locus in a three generation family with AD-FSP complicated by dementia and epilepsy. Assuming that both forms of AD-FSP are caused by mutations involving the same FSP gene, analysis of recombination events in this family positions the SPG4 gene within a 0 cM interval flanked by loci D2S2255 and D2S2347.

[A focus of multiple sclerosis in Bretagne: HLA markers and evaluation of consanguinity]. / Etude d'un foyer de sclérose en plaques en Bretagne: marqueurs HLA et évaluation de la consanguinité.

In a previous study, we established the overall prevalence of multiple sclerosis at 25 per 100,000 inhabitants in the French province of Brittany and found that the geographical distribution was uneven with four circumscribed high prevalence areas with more than 45 per 100,000. We conducted the present study to try to ascertain whether the existence of such clusters of MS could be explained by genetic factors, using two ways: the major histocompatibility markers and the frequency of intermarriage. Among the four areas of high prevalence, we examined the one with the highest prevalence, exempt from migratory movements over the last 100 years. We compared this studied population to a sample of 1005 healthy unrelated individuals coming from all over Brittany, designated as general Brittany population. A large sampling (about 25%) of the population accepted to take part in the study. Regarding HLA markers, we observed in the high prevalence area an increases percentage of B7, B8, B12, DR4 and a decreased percentage of B5, compared with the Brittany control population. The consanguinity coefficient in the population of high MS prevalence area was steadily much higher than the one in neighbouring areas with a low MS prevalence during a long period from 1896 to 1945. Under the reserve of non-randomized sampling of individuals for HLA marker study, our findings yielded a double argument in favor of genetic factors influencing the presence of clusters of MS cases: the particularities of HLA phenotype pattern and the increased consanguinity coefficient. The particularities of HLA polymorphism observed in the high prevalence area are likely to be the consequence of the intermarriage habits of this population.

[Long-term immunosuppression in multiple sclerosis: evaluation of treatments begun before 1972]. / Immunosupression au long cours dans la sclérose en plaques: évaluation des traitements commencés avant 1972.

Multiple sclerosis patients have been continuously treated by azathioprine. Only severe progressive forms were selected. The protocol of inclusion and follow-up is detailed. All cases started before 1972 have been reviewed, i.e. 102 cases. Of these 102, 35 stopped azathioprine during the first years and the reasons for this drop-out are analysed. Sixty seven treatments have been maintained for more than 5 years. An evaluation of these 67 patients through the Kurtzke scale shows that the 40 cases with a remittent progressive course have been stabilized as long as they were under treatment. Relapses were observed after discontinuing the therapy. In such cases azathioprine was restarted, leading again to stabilization. Twenty seven cases following a continuous progressive course at the time azathioprine was started showed no evidence of a benefit and kept on worsening. Complications related to treatment (as observed on 240 patients from 1967 to 1982) are detailed with special reference to infections, liver disease and malignancy. Even if the results observed on the course of severe remittent progressive forms of MS are in favor of continuous therapy by azathioprine, this should not be extended to all cases of MS at their first manifestation. It has to be limited to rapidly worsening cases, appreciated after a period of evaluation, when a threatening loss of autonomy may justify some limited risks.

[Urinary disorders in multiple sclerosis. Apropos of 47 cases]. / Les troubles urinaires dans la sclérose en plaques. A propos de 47 cas.

The authors report a series of 47 patients suffering from disseminated sclerosis who required neuro-urological management because of micturition disturbances. They were in general young (mean age 43 years) and had been suffering from disseminated sclerosis for 10 years (on average). The neurological disease was in general severe since it was progressive in 32 cases and pure remittent in 13 only. Two-thirds of the patients were autonomous from a locomotor standpoint. Micturition disturbances developed in the first five years of the disease in 2/ 3rds of the patients and became really troublesome only after disseminated sclerosis had been progressive for five years. Dysuria, frequency and incontinence with urgency were the commonest symptoms. Persistent or transient retention of urine remained relatively common. Nocturnal urine loss was rarer. Sphincter incompetence was marked in half of the patients but this did not necessarily go hand in hand with locomotor incapacity. Symptoms and signs were grouped as irritative, obstructive and mixed syndromes. From a urodynamic standpoint, the detrusor was sometimes normal but more often behaved pathologically, being either hyperactive or hypoactive. Hypoactivity of the detrusor was accompanied in 9 cases out of 10 by spasticity of the striate sphincter. Spasticity of the striate sphincter was the commonest type of behaviour, although normal striate sphincter electromyography was possible and; rarely, results were of peripheral neurogenic type. There was no evidence of any correlation between the type of micturition syndrome, detrusor function and striate sphincter function. Similarly, no correlation could be established between the type of detrusor dysfunction and the period for which disseminated sclerosis had been present.(ABSTRACT TRUNCATED AT 250 WORDS)

[Complement markers Bf and C4 in multiple sclerosis]. / Les marqueurs Bf et C4 du complément dans la sclérose en plaques.

Some immunogenetic HLA markers are significantly correlated with multiple sclerosis, e.g.: the antigens B7, DR2, and the associations B7-DR2, A3-B7-DR2. In addition, the polymorphism of the allotypes Bf and C4 is also controlled by chromosome 6; a study of these markers is therefore of interest. The study of Bf and C4 in multiple sclerosis included a population of genotyped unrelated patients: 50 patients for Bf markers and 41 for C4A and C4B markers. This study revealed an over-representation of allotype S and homozygous BfSS in multiple sclerosis. BfSS homozygote was significantly more frequent in the B7 negative and/or DR2 negative patients, i.e. when the risk markers per se were absent. No correlation could be evidenced with the remittent or progressive character of the disease. These data, obtained from the study of C4, are still preliminary ones. The results found with the Bf markers confirm the existence of a genetic factor in multiple sclerosis and suggest that the susceptibility gene of the disease could be closer to locus Bf than to locus DR.

[Epidemiology of multiple sclerosis in Brittany]. / Epidémiologie de la sclérose en plaques en Bretagne.

In the period 1976-1978 a study of the prevalence of multiple sclerosis in Brittany was conducted using data collected from hospital neurology units, Social Security offices and institutions for chronic patients. After elimination of double entries, analysis of these data showed a prevalence of 25 for 100 000 people. This was less than expected from estimates for northern France and from the known prevalences in the southern part of the British isles. When broken down according to the patients' place of residence, the figures were found to vary from one district to another, with four main foci: two near the coast, one inland and one in the town of Fougères. Disease-free areas were present near these foci.

HLA profiles in multiple sclerosis suggest two forms of disease and the existence of protective haplotypes.

261 multiple sclerosis (MS) patients were HLA-A and -B typed and 94 were HLA-D typed. The results were compared to those of controls typed for HLA-A; HLA-B (356) and HLA-D (113). We confirm and extend earlier findings (Oger et al. 1980b) that some phenotypes could modulate the expression of the MS susceptibility gene linked to B7-DR2: DR3 was found together with DR2 in 12/94 MS and only 3/113 controls and could be marker for an "augmentor" gene. In contrast, B35 and DR1 as well as B12 and DR7 could be markers of protector genes. We compared typing results of patients subgrouped on clinical features. 61 patients with progressive evolution showed increased A1, A1-B8, B8-DR3 and A1-B8-DR3 when compared to 200 patients with remitting evolution. When compared to controls both groups showed increased B7 but only the remitting group showed increased DR2. 71 patients with "benign MS" showed increased B7-DR2 and A3-B7-DR2. 54 patients with "severe disease" showed increased DR3 and A1-B8-DR3 when compared to controls. Both groups showed increased B7 (49.2% and 44.4% versus 25.5% for controls). 120 patients treated greater than 5 years with azathioprine were divided into "no progression" and "progression" while treated. Both groups showed increased B7 when compared to controls. DR2 was increased only in the "no progression" group. B8-DR3 and A1-B8-DR3 were found increased in the "progression" group only. We conclude that two forms of MS exist with different HLA profiles.

[Disseminated sclerosis. Possible correlation between clinical forms and HLA groups (author's transl)]. / Sclérose en plaques: corrélation possible entre formes cliniques et groupes H.L.A.

The study concerns HLA typing of 261 patients with disseminated sclerosis. All patients were grouped for loci A and B. In addition, 94 were typed in HLA DR and 132 in mixed lymphocytic culture (DW2 only). Analysis of tissue group distribution among patients compared with a control population showed not only over-representation of the B7, DW2, A3 B7 and B7 DR2 types (as previously stressed by several workers), but also of A9 and of B8 DR3 and A1 B8 DR3 associations. Moreover, it would seem that there are two distinct clinical forms of disseminated sclerosis, each form being characterized by a specific antigenic HLA association. Side by side with the conventional and most common "remittent" form, which is partly responsive to treatment, has a relatively favourable course and is frequently associated with B7 and DW2/DR2, there appears to emerge around DR3, B8 DR3 and A1 B8 DR3 a rarer, "progressive" form of rapidly increasing severity and resistant to immuno-suppressants. This, however, is a mere hypothesis which needs to be confirmed by further studies on a larger scale.

[Shy and Drager syndrome. Physiopathological and pharmacological approach based upon one case (author's transl)]. / Syndrome de Shy et Drager. Approche physiopathologique et pharmacologique à propos d'un cas.

The authors report a new case of Shy and Drager syndrome characterized by the severity of the extrapyramidal signs as well as that of orthostatic hypotension and urinary dysfunction. Peripheral adrenergic disturbance was proven, associated with an abnormality of the renin-angiotensin system. The authors describe the various drugs tried experimentally in treatment of the three main symptoms of the disease. A combination of Trihexyphenidyl and Dibenzepine finally appeared to be the most effective. Six months later, there remained a marked improvement in extrapyramidal signs and orthostatic hypotension. By contrast there was no improvement in urological symptoms.

Plasmatic renin activity in patients treated with L-dopa and inhibitor of dopa decarboxylase (IDC).

Plasmatic renin activity (PRA) was studied in patients receiving L-dopa, together with a decarboxylase inhibitor, at rest times and after periods of physical exertion. Although we can superimpose the results from unrelated Parkinson's disease patients on those of the control group, the results are inversed in stabilized patients (lowered PRA) and dyskinetic patients (increased PRA). There is a definite correlation between the increase in PRA and intensity of the dyskinesia. Dosage is the only other factor differentiating the two groups of Parkinsonians treated. The figures relative to arterial pressure are studied in the various groups.